Von Willebrands Disease (vWD) is the most common inherited bleeding disorder. We have studied the efficacy and feasibility of treating a child with type III severe vWD solely with cryoprecipitate prepared by repeated DDAVP-stimulated plasma exchange donation from a single, dedicated, paternal donor. An infant presented with massive hemorrhage at circumcision. The child was found to have FVIII:C 4 percent, FVIII:Ag 20 percent, vWF:RCo 21 percent, vWF:Ag 3 percent, indicative of severe vWD. His father carried an allele with a defect at the level of vWF mRNA expression but had a negative bleeding history with normal coagulation values. Cryoprecipitate was prepared from serial DDAVP-stimulated plasma exchange donation by the patient's father, using peripheral venous access, ACD-A anticoagulant, and autologous cryoprecipitate depleted plasma as replacement fluid. During the first 14 years of the patient's life, the father underwent 53 plasma exchange donations, yielding a total of 139,307 units of FVIII. In the past year, plasma exchange donation was standardized to involve processing of exactly 4,500 mL of plasma, which yielded a mean of 14 bags of cryoprecipitate, each having a FVIII content of approximately 330 units. Repeated plasma exchange donation was well tolerated, with adverse effects including mild headache and flushing due to the DDAVP and citrate toxicity. Cryoprecipitate was stored for up to 102 months at -70C. 90 percent of the cryoprecipitate was transfused after 1 year of storage, with a mean collection to transfusion interval of 2.4 years. Cryoprecipitate tested after 13 to 77 months of storage showed 48 to 124 percent of the original FVIII activity; decreased activity was noted with increasing length of storage. Manufacture of plasma exchange donation-derived FVIII resulted in an estimated 50 percent cost reduction compared with similar doses of commercial factor concentrates. All bleeding episodes that occurred in the patient since birth were managed with cryoprecipitate derived by this method. At age 14, the child has received only one donor exposure throughout his life, that of the paternal donor of his cryoprecipitate. Cryoprecipitate prepared by repeated plasma exchange donation of a vWD carrier provided excellent hemostatic function, even after prolonged storage intervals of greater than 1 year. Plasma exchange donation of a committed donor may be the safest option for long-term management of vWD, and provides a cost-effective alternative to commercial factor concentrates.